Metal Carbenoid Ring Opening of 2-alkyl and Alkoxy Furan-Synthesis, Application and SAR of 1,6-Dioxo-2,4-diene Derivatives

by Shieh, Po-Chuen

Abstract 2-Methoxy- and 2-trimethylsilyloxyfuran undergo facile ring opening reaction upon treatment with metal carbeniod. Treatment of 2-methoxy-furan with ethyl diazoacetate and aryl-£\-diazocarbonyl compounds under metal catalysis afford (Z,E)-2,4-hexadienedioate and aryl-6-oxo-2,4-hexadienoates respectively. When 2- trimethylsilyloxyfuran was used, desilylation occurred to give directly the monoprotected (Z,E)-muconic acid and 6-aryl-6-oxo-2,4-hexadienoic acids. We have synthesized aromatic dienyl diketone using the method of Wenkert from aromatic diazo ketone and 2-methylfuran. This method was found to give a mixture of (Z,E)/(E,E)-dienyl diketones. The anticancer, antibacterial and vasorelaxing activities are evaluated. All the aromatic dienyl diketones synthesized exhibit strong in vitro inhibition of tumor cell and micro0organisms growth respectively, and three of these compounds exhibit strong vasorelaxing effect. Reaction of 1,6-dioxo-2,4-diene with P2S5 and Lawesson¡¦s reagent affords the 2,5-disubstituted thiophene. This reaction can take place regioselectively in the presence of BF3-etherate catalysis, useful for the synthesis of arylthiophene. We have demonstrated a new methodology for the facile synthesis of arylthiophene.